Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

Michael A. Turner; Hannah M. Hollandsworth; Hiroto Nishino; Siamak Amirfakhri; Thinzar M. Lwin; Andrew M. Lowy; Sukhwinder Kaur; Gopalakrishnan Natarajan; Kavita Mallya; Robert M. Hoffman; Surinder K. Batra; Michael Bouvet

doi:10.21873/invivo.12676

Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

Michael A. Turner, Hannah M. Hollandsworth, Hiroto Nishino, Siamak Amirfakhri, Thinzar M. Lwin, Andrew M. Lowy, Sukhwinder Kaur, Gopalakrishnan Natarajan, Kavita Mallya, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. Results: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). Conclusion: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

Original language	English (US)
Pages (from-to)	57-62
Number of pages	6
Journal	In Vivo
Volume	36
Issue number	1
DOIs	https://doi.org/10.21873/invivo.12676
State	Published - Feb 2022

Keywords

Antibody
Fluorescence guided surgery
MUC5AC
Mucin
PDOX
Pancreatic cancer
Tumor-specific imaging

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Cancer Research
Pharmacology

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title = "Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft",

abstract = "Background: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. Results: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). Conclusion: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.",

keywords = "Antibody, Fluorescence guided surgery, MUC5AC, Mucin, PDOX, Pancreatic cancer, Tumor-specific imaging",

author = "Turner, {Michael A.} and Hollandsworth, {Hannah M.} and Hiroto Nishino and Siamak Amirfakhri and Lwin, {Thinzar M.} and Lowy, {Andrew M.} and Sukhwinder Kaur and Gopalakrishnan Natarajan and Kavita Mallya and Hoffman, {Robert M.} and Batra, {Surinder K.} and Michael Bouvet",

year = "2022",

month = feb,

doi = "10.21873/invivo.12676",

language = "English (US)",

volume = "36",

pages = "57--62",

journal = "In Vivo",

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publisher = "International Institute of Anticancer Research",

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T1 - Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

AU - Turner, Michael A.

AU - Hollandsworth, Hannah M.

AU - Nishino, Hiroto

AU - Amirfakhri, Siamak

AU - Lwin, Thinzar M.

AU - Lowy, Andrew M.

AU - Kaur, Sukhwinder

AU - Natarajan, Gopalakrishnan

AU - Mallya, Kavita

AU - Hoffman, Robert M.

AU - Batra, Surinder K.

AU - Bouvet, Michael

PY - 2022/2

Y1 - 2022/2

N2 - Background: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. Results: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). Conclusion: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

AB - Background: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. Results: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). Conclusion: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

KW - Antibody

KW - Fluorescence guided surgery

KW - MUC5AC

KW - Mucin

KW - PDOX

KW - Pancreatic cancer

KW - Tumor-specific imaging

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Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

Abstract

Keywords

ASJC Scopus subject areas

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